Isoleucine--tRNA ligase, mitochondrial

Isoleucine–tRNA ligase, mitochondrial (IARS2) is an aminoacyl-tRNA synthetase that catalyzes the specific attachment of isoleucine to its cognate mitochondrial tRNA(Ile), a critical step in mitochondrial protein synthesis (UniProt: Q9NSE4). The protein functions in mitochondrial translation and is expressed across tissues. A rare autosomal recessive disorder, CAGSSS (cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia), is associated with IARS2 mutations, highlighting its importance in developmental and neurological processes (UniProt: Q9NSE4).

In Alzheimer's Disease, IARS2 is modestly upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of +0.22 across analyzed subcellular fractions in TMT-labeled proteomics (Chaparral AD proteomics). This upregulation may reflect compensatory mitochondrial protein synthesis activity or stress responses in AD pathology, though the biological significance of this modest increase requires further investigation.